Topics:

RAV12 Monoclonal Antibody Promising in GI Cancers

RAV12 Monoclonal Antibody Promising in GI Cancers

NEW YORK—In a phase I study, the chimeric monoclonal antibody, RAV12 (Raven biotechnologies inc) has shown preliminary evidence of efficacy in gastrointestinal (GI) tumors. Howard A Burris III, MD, director of drug development at the Sarah Cannon Cancer Center, Nashville, one of three centers where the trial is underway, spoke about the research at the Chemotherapy Foundation Symposium XXIV.

"It's always exciting to be involved in the development of a first-in-man compound. This is clearly different from many other antibodies that target growth factors," Dr. Burris said. "With the RAV12 antibody, we're looking, specifically, at being able to provide a direct cytotoxic effect."

The antibody targets the RAAG12 antigen and kills cells through oncosis rather than apoptosis (see box, The Science Behind the Study). "While RAV12 binds to some normal GI epithelial cells, it is more broadly distributed on membranes of tumor cells," he said.

The open-label dose-escalation study includes patients with metastatic or recurrent, histologically confirmed adenocarcinoma of GI origin, or another tumor type if RAAG12 positive. Patients must have had one to three prior therapies. Treatment continues until disease progression or unacceptable toxicity.

Dr. Burris reported on four treatment cohorts totaling 24 patients: The first 21 patients received RAV12 in escalating weekly intravenous doses of 0.3 mg/kg to 1.5 mg/kg over 4 weeks. Adverse events included liver function test (LFT) abnormalities, which were transient at the lower doses but more persistent at the highest dose, and infusion-related abdominal pain requiring management, which also appeared to be dose related.

Dr. Burris said the abdominal pain and LFT abnormalities may be related to Cmax. "There is recurrence with each dose, and there is a trend toward resolution between doses. Cmax can be altered by changing administration, lengthening the infusion, or fractionating the dose," he said.

To deliver a RAV12 dose equivalent to 1.5 mg/kg/wk, since efficacy is seen at this dose, fractionated dosing two to three times a week is being explored in the ongoing phase I trial. Dr. Burris' report included three patients who received

Pages

 
Loading comments...
Please Wait 20 seconds or click here to close